This competing renewal outlines experiments that combine the powerful molecular genetics of the model plant Arabidopsis with cell biological approaches to examine the function of several key genes involved in pathogenesis-associated programmed cell death (PCD) regulation and execution. Understanding the control of PCD is important for developing strategies to manipulate PCD to prevent or cure diseases involving excess or insufficient PCD induction. Known in plants as the "hypersensitive response" (HR), PCD aids in limiting the spread of some pathogens and/or amplifying other defenses. Plants have a second, slower PCD response, called susceptible cell death, that facilitates pathogen growth and transmission and is triggered by pathogens that do not cause an HR. Both types of PCD are subject to genetic control and in some cases both require a common signaling molecule called salicylic acid (SA). However, initiation of the HR in response to some pathogens does not require SA. These observations have raised important questions as to whether the regulation and/or execution of PCD occurs by multiple independent mechanisms or whether there are some core steps. To address these questions and to elucidate the steps required for the control of PCD associated with the HR and susceptible cell death, several genes termed ACCELERATED CELL DEATH (ACD) important for cell death and defense regulation were identified. The proposed research addresses the mechanism of action of a novel SA-dependent signaling component of the cell death and disease resistance pathway called ACD6, the characterization of the SA-dependent ACD5 gene important for cell death during disease and the determination an SA-independent mechanism whereby chlorophyll catabolites, structurally related to the PCD-inducing protoporphyrin IX in animals, induce cell death during disease. A more open ended aspect of the research program is the identification of additional genes, through the employment of genetic screens, important for the positive and negative regulation of cell death that occurs during disease and the HR. Finally, an important goal is to exploit the acd and other mutants in the development of cell biological assays to directly visualize and study the properties and signaling requirements of single dying cells and to determine the involvement of mitochondria and/or chloroplasts in coordinating PCD.